Chronic liver injury leads to the development of liver fibrosis for which there is no therapy. We have shown that phosphodiesterase 4 (PDE4) plays a pathogenic role in the development of hepatic fibrosis in a rat model of cholestatic liver injury. However, the involvement of PDE4 enzymes in hepatic fibrosis occurring in other forms of liver disease has not been examined. Here, we tested the effect of PDE4 inhibition on fibrogenesis in a mouse model of carbon tetrachloride (CCl4) induced fibrosis. Liver tissue proteomic and phosphoproteomic analysis was performed to identify the relevant novel proteins affected by PDE4 inhibition.