Our aim was to gain insight into the gene expression profile during hepatic fibrosis autoreversal. Spontaneous recovery from hepatic fibrosis was created in SD rats by CCl(4) exposure for 8 weeks and then withdrawal for 6 weeks. Then differentially expressed genes during regression of fibrosis were analyzed using cDNA microarray. Results obtained were further subjected to hierarchical clustering and validated by semiquantitative RT-PCR. Expression of Mapk1 and Rps6ka1, which are critical members of the mitogen-activated protein kinase (MAPK) signaling pathway, was also investigated by Northern blot and immunohistochemistry. Microarray hybridization identified 254 genes differentially expressed throughout resolution of fibrosis. Being verified by RT-PCR, up- or down-regulated genes were classified into various groups according to clustering and function: (1) metabolic enzymes, (2) facilitated diffusion proteins/transporters/symporters, (3) gastrointestinal hormones/receptors, (4) lipoproteins/fatty acid binding proteins, (5) transcription factors/nuclear factors, and (6) the MAPK signaling pathway. The mRNA level of Mapk1 increased greatly as hepatic fibrosis reversed. Meanwhile Mapk1 and Rps6ka1 were proven to be expressed in hepatocytes and absent from mesenchymal cells. Six groups of genes exhibit a close relation to the recovery of CCl(4)-induced hepatic fibrosis. The MAPK signaling-dependent pathway, representing one of the gene groups, may contribute to the reversal of hepatic fibrosis.