Objective To investigate the effects of glycyrrhizin on genes expression during the process of rat liver fibrosis. Methods Rat models of liver fibrosis were obtained by subcutaneous injections of CCl 4, another group were treated with both CCl 4 and glycyrrhizin. A control rat, a CCl 4 induced liver fibrosis rat and a glycyrrhizin treated rat were chosen to undergo cDNA microarray respectively. According to the results of cDNA microarray, a gene (smurf2) abnormally expressed in the liver fibrosis rat and expressed normally in the treated group was chosen to study its changes at different stages of experimental liver fibrosis by semi-quantitative RT-PCR. Results Many genes including smurf2, PTAFR, CYP2D6, FGG associated with inflammation and metabolism were identified increased expression in the CCl 4 treated group and normal expression in the glycyrrhizin group by cDNA microarray. Semi-quantitative RT-PCR showed after 1 week there were no differences of smurf2 gene expression levels among the three groups, after 2 weeks smurf2 gene expression levels decreased both in the CCl 4 group and glycyrrhizin group, after 4 weeks smurf2 gene expression levels increased in the CCl 4 group but decreased in glycyrrhizin group, after 8 weeks smurf2 gene expression levels decreased again in the CCl 4 group but increasd to the normal level in the glycyrrhizin group. Conclusion By cDNA microarray, we found the effects on the changes of smurf2 gene expression may contribute to the anti-fibrosis molecular mechanism of glycyrrhizin.