Objective To investigate the selective injury of inflammation on dopaminergic neurons in the substantia nigra in rat brain. Methods Ten healthy male SD rats were randomly assigned into 25μg lipopolysaccharide (LPS)-injected (experimental) group and the salineinjected (control) group. Either LPS or saline was injected into the lateral cerebral ventricle on the right side. Immunohistochemistry staining was used to observe either the activity of microglia or neuronal loss in different neurons of the brain, including dopaminergic neurons in the substantia nigra (SN) and serotonergic neurons in the dorsal raphe nucleus (DRN). The cholinergic neurons in the basal nucleus of Meynert (BN) were shown by enzyme histochemistry. Results The immunohistochemistry staining demonstrated that considerable microglia were activated in almost whole brain, especially in the striatum, hippocampus, SN and DRN. The staining for three different types of neurons indicated that the number of dopaminergic neurons in the SN in the experimental group decreased 40.1% (EM>P/EM><0.01), compared with that in the control group, and no such significant changes were seen in cholinergic neurons in the BN and serotonergic neurons in the DRN. Conclusion Intracerebroventricular administration of LPS can induce an inflammation in the brain and which can induce a selective injury of dopaminergic neurons in the substantia nigra.