Objective To explore the effect of interlukin-10 (IL-10) on interlukin-6 (IL-6) and signal transducer and activator of transcription 3 (STAT3) in rats with sepsis-induced lung injury. Methods The animal model of sepsis was set up by cecal ligation and puncture (CLP) in 120 Wistar male rats, which were randomly divided into 3 groups: control group (C group), CLP group and IL-10 treatment group (IL-10 group). At 2, 6, 12, 24h after CLP, IL-6 concentration in lung homogenate was detected by enzyme linked immunosorbent assay (ELISA). Lung IL-6, inducible nitric oxide synthase (iNOS) mRNA were detected with real-time fluorescent quantitative polymerase chain reaction (real-time RT-PCR), DNA-binding activity of STAT3 was analyzed by electrophoretic mobility shift assay (EMSA). Nitric oxide (NO) level in lung tissue was determined by spectrophptometry. Results The expressions of IL-6 (409.42±12.34) vs (175.14±12.34) , IL-6 mRNA( 0.37±0.02) vs (0.09±0.01), DNA-binding activity of STAT3 (46.81±2.52) vs (1.75±0.20), NO level (5.82±0.09) vs (4.72±0.11) and iNOS mRNA (2.61±0.04) vs (1.04±0.02) in lung homogenate in CLP group were higher than those in C group at 2 hours after operation (P<0.05), the trend of which last for 12h (P<0.05). The expressions of IL-6, IL-6 mRNA, DNA-binding activity of STAT3, NO level and iNOS mRNA in lung tissues in IL-10 group were reduced as compared with CLP group (P<0.05). Conclusion IL-10 may attenuate lung injury in CLP-induced septic rats through inhibiting the IL-6/STAT3 signaling pathway.