Objective To observe the effect of lidocaine plexus block on cognitive function, stress response and pain in rats after laparotomy, and explore possible mechanisms. Methods A total of 48 SD rats were used to establish a laparotomy model. According to the random number table method, they were divided into two groups (n=24): a control group and a plexus block group. The plexus block group was injected with a bolus of 0.5% lidocaine (2 ml) in retroperitoneal tissue, while the control group was injected with a bolus of the same volume of normal saline at the same site. At postoperative 6, 12, 24 h and 48 h, the T maze test was used to evaluate cognitive function. At postoperative 6, 12 h, and 24 h, pain indicators were detected by a thermal pain tester, serum stress response indicators were examined by enzyme linked immunosorbent assay (ELISA), serum oxidation indicators were measured by the thiobarbituric acid method and the xanthine oxidase method, and the expression of nuclear factor E2‑related factor 2 (Nrf2) and heme oxygenase‑1 (HO‑1) protein in the hippocampus was detected by Western blot. Results Compared with the control group, the plexus block group showed increases in the success rate of the T maze test at postoperative 6, 12, 24 h and 48 h; increases in heat pain threshold, serum malondialdehyde (MDA) level, and Nrf2 and HO‑1 protein level in the hippocampus, and decreases in the levels of serum C‑reaction protein (CRP), glucocorticoid (GC) and adrenocorticotropic hormone (ACTH), and superoxide dismutase (SOD) activity at postoperative 6, 12 h and 24 h (P<0.05). For the control group, compared with those at postoperative 6 h, remarkable decreases were found in the success rate of the T maze test at postoperative 12, 24 h and 48 h; in the threshold of heat pain and the level of ACTH at postoperative 12 h and 24 h and in the level of serum GC at postoperative 24 h (P<0.05); while increases were seen in the levels of serum CRP and MDA, SOD activity, and the levels of Nrf2 and HO‑1 protein in the hippocampus at postoperative 12 h and 24 h, and in GC at postoperative 12 h (P<0.05). For the control group, compared with those at postoperative 12 h, significant increases were found in the success rate of the T maze test at postoperative 24 h and 48 h, and in the threshold of heat pain and the level of serum CRP at postoperative 24 h (P<0.05), while decreases were seen in the levels of serum GC, ACTH, MDA, SOD activity, Nrf2 and HO‑1 protein levels in the hippocampus at postoperative 24 h (P<0.05). Compared with those at postoperative 24 h, the success rate of T maze test in the control group increased at postoperative 48 h (P<0.05). For the plexus block group, compared with those at postoperative 6 h, remarkable decreases were found in the success rate of the T maze test at postoperative 12, 24 h and 48 h, and in the threshold of heat pain, serum ACTH and GC at postoperative 12 h and 24 h (P<0.05); while increases were seen in serum CRP level, MDA level, SOD activity, Nrf2 and HO‑1 protein levels in the hippocampus at postoperative 12 h and 24 h (P<0.05). For the plexus block group, compared with those at postoperative 12 h, significant increases were found in the threshold of hot pain, and serum CRP and GC levels at postoperative 24 h (P<0.05), while decreases were seen in the success rate of the T maze test at postoperative 24 h and 48 h, and in serum ACTH and MDA levels, SOD activity, and Nrf2 and HO‑1 protein levels in the hippocampus at postoperative 24 h (P<0.05). Compared with those at postoperative 24 h, the success rate of the T maze test in the plexus block group decreased at postoperative 48 h (P<0.05). Conclusion Nerve plexus block by lidocaine can weaken the influence on cognitive function of rats after operation, relieve pain and postoperative stress response, and inhibit oxidative stress.