Objective To explore inhibition of nicotine on apoptosis of chondrocytes induced by monosodium iodoacetate (MIA). Methods Rat primary chondrocytes were isolated by enzyme digestion, and the cells were treated with 10^-8, 10^-7, 10^-6, 10^-5 mol/L nicotine for 48 h. The cases were randomly divided into five groups, except for normal group, the other four groups were treated with 4 μmol/L MIA 24 h, and three groups were treated 10^-8, 10^-7, 10^-6 mol/L nicotine. The viability of chondrocytes was detected by MTT assay. The apoptosis of chondrocytes was examed by Annexin V-FITC/PI flow dual-staining method. The activity of cysteinyl aspartate specific proteinase 3 (Caspase 3) was measured by spectrophotography method. The activation of phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) and the expression of down-stream molecule Bax, Bcl-2 was assayed by western blot. Results 10^-7, 10^-6 mol/L nicotine increased chondrocytes' viability (P < 0.05), 10^-5 mol/L nicotine reduced chondrocytes' viability (P < 0.05), and 10^-8 mol/L nicotine didn't effect on chondrocytes' viability (P > 0.05). 10^-8, 10^-7, 10^-6 mol/L nicotine could increase MIA-induced chondrocytes' viability (P < 0.05), suppress MIA-induced chondrocytes' apoptosis and the activity of MIA-induced Caspase 3 (P < 0.05). Moreover, 10^-7, 10^-6 mol/L nicotine could increase the expression of PI3K and phosphorylation of AKT (P < 0.05), down-regulate the expression of Bax and up-regulate the expression of Bcl-2 in MIA-induced rat chondrocytes (P < 0.05). Conclusion These results suggested nicotine could exert anti-apoptosis in MIA-induced rat chondrocytes, which might be related to PI3K/AKT signal pathway.