This study investigated the effects of propofol on the mRNA expression of Toll-like receptor-4 (TLR4) in BV-2 cells during mimic ischemia-reperfusion (I/R) injury in vitro. BV-2 cells, a mouse microglia line, were cultured and divided into 4 groups at random: control group (group C), ischemia/reperfusion group (group I/R), low-dose propofol (25 micromol/L) intervention group (group PF(25)) and high-dose propofol (100 micromol/L) intervention group (group PF(100)). The mRNA expression of TLR4 and NF-kappaB was measured by means of RT-PCR. TNF-alpha levels in the supernatants of BV-2 cells were detected by ELISA. The results showed that the mRNA expression of TLR4 and NF-kappaB was significantly higher in groups I/R, PF(25) and PF(100) than in group C (P<0.01). And the TNF-alpha level in the supernatants was elevated in groups I/R, PF(25) and PF(100) as compared with that in group C (P<0.01). After pre-treatment with propofol, the mRNA expressions of TLR4 and NF-kappa B and the TNF-alpha level were significantly decreased in groups PF(25) and PF(100) in comparison to those in group I/R (P<0.01). And the decrease in those indicators was more significant in group PF(100) than in group PF(25) (P<0.01). It was concluded that propofol exerted brain-protecting effects during I/R injury by suppressing the mRNA expressions of TLR4 and NF-kappaB and deceasing the TNF-alpha level.