Objective To investigate the effect of minocycline on inflammation-induced dopaminergic neurodegeneration. Methods SD rat model of inflammation-induced dopaminergic neurodegeneration was established in mesencephalic neuron/glia cultures by lipopolysaccharides. The culture system was treated by minocycline before or after the addition of lipopolysaccharides. The number of dopaminergic neurons was determined by immunocytochemistry and cell counting. Cell bioactivity was detected by liquid scintillation uptake assay. Besides, the changes of key proinflammatory factors such as tumor necrosis factor-α (TNF-α)(by ELISA), interleukin-1β (IL-1β)(by ELISA), nitric oxide (NO)(by Griess method) and superoxide (by cytochrome C reduction method) were examined in the cultures. Results Minocycline (2-10 μmol/L) pretreatment dose-dependently attenuated the reduction in dopamine uptake and dopaminergic cell number in mesencephalic cultures treated with lipopolysaccharides (1-100 ng/mL). Minocycline (10 μmol/L) posttreatment also protected dopaminergic neurons from lipopolysaccharides (10 ng/mL)-induced neurodegeneration in neuron/glia cultures. Minocycline pretreatment and posttreatment significantly inhibited the production of TNF-α, IL-1β, NO and superoxide in neuron/glia cultures. Conclusion Minocycline may protect mesencephalic dopaminergie neurons treated with lipopolysaccharides by inhibiting the production of proinflammatory factors.