Murine cytochrome P450 2A5 (CYP2A5) is induced during hepatotoxicity and hepatitis, conditions which are generally associated with depression of hepatic CYPs. This study investigated the influence of non-parenchymal liver cells and pro-inflammatory cytokines on the regulation of hepatic CYP2A5 expression. Individual pro-inflammatory cytokines IL-1β, IL-6, TNF-α, TGF-β, and IFN-γ, did not influence CYP2A5 mRNA expression in cultured primary mouse hepatocytes. Non-parenchymal cells which may release cytokines during hepatic injury also did not contribute to CYP2A5 mRNA induction in pyrazole-treated hepatocyte cultures. A reduction in CYP2A5 mRNA levels was observed in lipopolysaccharide-treated (LPS) cultures and also in LPS-treated mice. Serum alanine aminotransferase levels were elevated in mice treated with pyrazole at a dose that resulted in an induction of CYP2A5. These results demonstrate that treatment with various pro-inflammatory cytokines and LPS does not increase CYP2A5 expression in mouse hepatocytes suggesting that hepatotoxicity, rather than hepatitis, is required for the induction of CYP2A5.