Abstract： Objective To investigate the inhibitory effect of minocycline (Mino) on lipopolysaccharide (LPS)-induced activation ofmicroglias and its srbsequent protective effects on nigral dopaminergic neurons. Methods A total of 25 male Sprague-Dawley (SD) rats were randomly allocated into three groups, sole LPS intervention group (LPS group)(n=10), LPS+Mino intervention group (n=10)(LPS+Mino group) and 5 rats injected with normal saline as the control group. Behavioral changes of all the rats were observed at 7 and 14 d, and the immunohistochemistry, in situ hybridization and Western blot were applied to observe the activation of microglias and the expression levels of positive neurons, mRNA and protein of tyrosine hydroxylase (TH) and OX-42. Results The rotation time of the LPS+Mino group was significantly lower than that of the LPS group at 7 and 14 d; the majority of microglias were activated in both the LPS and LPS+Mino groups, and the number of "amoeboid" microglias in the latter group was obviously lower than that in the former group, a few "ramified" microglias still existing in the latter group; Western blot assay showed that the protein levels of OX-42 expressed in the operative side midbrain of the two groups after induction were significantly higher than that in the control group, and the increment of (0.91±0.04) in the LPS+Mino group was significantly lower than that of (1.03±0.03) in the LPS group (P＜0.01); the number of TH positive neurons and the levels of TH mRNA and protein in the operative side midbrain of both groups after LPS treatment were obviously lower than in the control group, and the decreases of (21.54 ±4.89,39.87 ±7.03and 0.42±0.03) in the LPS group were significantly higher than that of (53.41±8.36,65.12±9.06 and 0.63±0.04) in the LPS+Mino group (P＜0.01). Conclusion Mino may protect nigral dopaminergic neurons against lipopolysaccharide-induced neurotoxicity by inhibiting microglia activation and subsequently prevent the progression of LPS-induced Parkinson's disease (PD).[ Key words ] Minocycline; Lipopolysaccharide; Dopaminergic neurons; Microglia;Parkinson's disease