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Objective To investigate the effect of propofol on the expression and phosphorylation of the skeletal muscle insulin receptor and its substrates following hepatic ischemia-reperfusion injury (HIRI). Methods Sixty healthy Wistar rats were divided randomly into a propofol group (P) and an ischemia-reperfusion group (I/R). Rats in the P group received propofol infusion prior to ischemia and during a 120-minute post-reperfusion period. Plasma glucose and insulin concentrations were measured, as well as expression levels of the insulin signaling proteins insulin receptor (IR) β unit (IRβ) and IR substrate 1 (IRS-1). In addition, tyrosine phosphorylation levels of these proteins were measured in skeletal muscle. Results Plasma glucose levels in the two groups were higher at 2 hours after reperfusion (T2) versus exposure of the hepatic hilum (T1). Plasma glucose levels in the I/R group were higher than those in the P group, while insulin levels at T2 were lower. In addition, phosphotyrosine levels of IRβ and IRS-1 were decreased by 32.1% and 22.4%, respectively. Conclusion Propofol increased phosphotyrosine levels of IRβ and IRS-2, resulting in an alleviation of increased plasma glucose levels following HIRI.