Objective To observe the role of Toll like receptor 4 (TLR-4) in the alternation of nigral-striatal dopamine system and innate immunity in postnatal brains following prenatal exposure to lipopolysaccharide (LPS). Methods A total of 15 timed-pregnant TLR-4 deficient C57BL/10ScNCr mice and 15 wild type (WT) C57BL/10ScSn mice at embryonic day 10.5 (E10.5) were used in this study. The mouse was injected intraperitoneally with LPS or TLR-2 ligand peptidoglycan (PDG) or saline. A total of 5 brains with different prenatal exposure and TLR-4 genotyping were harvested at postnatal day of 120.The dopaminergic (DA) neurons and microglial cells were quantified by immunohistochemistry staining and sterology. Striatal DA content and DA metabolites were measured by high performance liquid chromatography (HPLC). Luminex 100 multiplex cytokine assay was used to determine the protein levels for the cytokines tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β). Results Compared to the saline control, a prenatal LPS exposure led to a (25.3±2.1)% reduction of DA neurons in the postnatal substantia nigra (SN) of 4-month-old C57BL/10ScSn mice, which was associated with reduced striatal DA level (33.5±5.0)% and an increase in homovanillic acid to DA ratio. Moreover, the prenatal LPS exposure resulted in an increase of the total number of microglia (294±24) %and the elevation of TNF-α and IL-1β in striatum and SN. On the contrary, there were no significant changes of SN DA neurons and inflammatory response in postnatal brain of C57BL/10ScNCr mice prenatally exposed to LPS. Prenatal PDG exposure led to similar alternations of nigralstriatal dopamine system and innate immunity in postnatal brains of both C57BL/10ScNCr and C5