Objective To evaluate the effects of DA‑JC4 pretreatment on the cognitive function of sleep‑deprived elderly rats.Methods A total of 36 healthy male SD rats, aged 18‒22 months and weighing 500‒600 g, were divided into three groups according to the random number table method (n=12): a control group (group C), a sleep deprivation group (group S) and a DA‑JC4 group (group D). The sleep deprivation model was established using elderly rats in group S and D in a modified multi‑platform water environment. Rats in group D were intraperitoneally injected with 25 nmol/kg DA‑JC4 (dissolved in 1 ml normal saline) at 10:00 per day for consecutive six days. Those in groups C and S were intraperitoneally injected with the same volume of normal saline. After sleep deprivation, the rats were subjected to a Morris water maze experiment for four consecutive days, the times of crossing the platform and the time of staying in the target quadrant were recorded. At the end of the water maze experiment on day 5, the rats were sacrificed and the hippocampal tissues were taken. The levels of interleukin‑1β (IL‑1β) and tumor necrosis factor‑α (TNF‑α) were detected by enzyme linked immunosorbent assay (ELISA), and the expression of nuclear protein nuclear factor kappa‑B (NF‑κB) p65 was measured by Western blot. Results Compared with group C, rats in groups S and D had less crossing times, shorter residence time in the target quadrant, increased levels of hippocampal IL‑1β and TNF‑α, and up‑regulated expression of NF‑κB p65 (P<0.05). Compared with group S, group D presented increased crossing times, prolonged residence time in the target quadrant, decreased levels of IL‑1β and TNF‑α in the hippocampus, and down‑regulated expression of NF‑κB p65 (P<0.05). Conclusions DA‑JC4 pretreatment improves the cognitive function of sleep‑deprived older rats, which may be associated with suppression of hippocampal inflammation.