[Objective]To investigate the effect of extracellular signal-regulated kinase(ERK) on PHA-induced USP22 expression in human peripheral blood mononuclear cells(PBMCs).[Methods]PBMCs were treated with or without ERK inhibitor PD98059(10μmol/L) for 30 min,followed by PHA treatment(1,10,100 mg/L) for 24 hours. The USP22 protein expression and the phospho-ERKl/2 level in cell lysate were detected by Western blot while mRNA was detected by RT-PCR.[Results]PHA stimulated ERK1/2 phosphorylation and USP22 expression in PBMCs.Pre-treatment with ERK inhibitor PD98059 partially blocked PHA-induced USP22 mRNA and protein expressions. [Conclusions]ERK 1/2 signal pathway is involved in PHA-induced USP22 expression in PBMCs.