Objective: To explore the inhibitory effect of minocycline (MC) on lipopolysaccharide-induced production of nitric oxide(NO) and expression of induced nitricoxide synthase(iNOS) in BV-2 microglial cells and its molecular mechanisms. Methods: The BV-2 microglial cells were treated with LPS (100 ng/ml) or various concentrations of minocycline (0,0.1,1,10,100 μmol/L). Accumulated NO was measured in the cell supernatant by enzyme method,iNOS protein and mRNA were examined by immunochemistry staining and RT-PCR technique,respectively. p38MAPK protein was examined by Western blot in BV-2 cells. Results: The NO production and iNOS protein and mRNA levels were significantly increased in LPS group than those of the control group(P < 0.05, 0.01,0.01,respectively). The pre-treatment of MC(10 μmol/L) significantly inhibited the NO production and the increments of iNOS protein and mRNA induced by LPS. The NO contents and the levels of iNOS protein and mRNA in MC+LPS group were significantly lower than those of the LPS groups (all P < 0.01),but still significantly higher than those of the control group (all P < 0.05). There was not significant differences of total p38MAPK protein expression in all groups,but no phospho-p38MAPK proteins were detected in the control group and MC group. The level of phospho-p38MAPK in the control group was significantly lower than that of the LPS group (P < 0.01),in which the increased phospho-p38MAPK level was reversed by MC (P < 0.01),Conclusion: The pre-treatment of MC could significantly inhibit the NO production and the increase of iNOS protein and mRNA induced by LPS through inhibiting the p38MAPK pathway in microglial cell.