Objective:To study the protective effects of nicotine on cartilage of monoiodoacetic acid(MIA)-induced rat osteoarthritis model. Methods:A total of 40 rats were randomly divided into four groups(control group,MIA group,MIA+Nic 0.25 mg/kg group and MIA+Nic 0.5 mg/kg group). Each group rats were sacrificed on 30th day after they received the first intra-articular injection of MIA(1mg) surgery. The right knee samples were carefully dissected. Generally light microscope and histological pathological examination were used to observe the destruction of articular cartilage. Reverse-transcription PCR was used to detect the gene expression of type II collagen and aggrecan. The protein expression of phosphor-Akt was measured by Western blot test. Results:Compared with the MIA group,nicotine treatment significantly decreased the light microscopy score and the Mankin’s score(P < 0.01) of the knee samples,and significantly increased the mRNA levels of typeⅡ collagen and aggrecan (P < 0.01) and the protein levels of phosphor-Akt (P < 0.01). Conclusion:Nicotine attenuates the severity of cartilage degeneration in the experimental rat model. These protective effects may partially benefit from the increase of phosphor-Akt expression.