We previously reported that the strain difference in the development of porcine-serum (PS)-induced rat hepatic fibrosis was closely related to the difference in the mode of MHC class-II-related genes expression. This study was carried out to clarify the serological and immunohistochemical changes in this hepatic fibrosis model. Six-week-old male Brown Norway (BN) and Wistar rats were injected with 0.5 ml of sterile PS twice a week for up to 8 weeks. The serum levels of PS-specific IgG1, IgG2a, and IgM were elevated more prominently in BN rats than Wistar rats. In the liver, significant increases in the numbers of PS-, OX-6 (RT1.B)-, CD4-, CD8, ED1-, and ED2-positive cells occurred earlier in BN rats than Wistar rats. At 8 weeks, deposition of PS and immunoglobulins was observed in hepatic fibrous septa and renal glomerular mesangium, and IgG1- and IgG2a-positive cells were found in the white pulp of the spleen. The present results suggest that humoral immunity probably regulated by MHC class II molecules and inflammatory cells may be involved in PS-induced hepatic fibrosis in rats.