| The aim of this study was to determine the biochemical changes in the infected buffaloes with fasciolosis. Also, the current study recognized the gross and histopathological changes resulting from the invasive Fasciola spp. in the liver and gallbladder. The biochemical results showed statistically significant increases in the serum total bilirubin, creatinine, and active serum enzymes ALT, AST, ALP, and GGT. In contrast, the serum total albumin showed a significant decrease in infected buffaloes. Moreover, the results of the gross pathological examination revealed that cirrhosis and paleness of the liver with multiple abscesses appearing as pale necrotic areas, as well as thickness and calcification with fibrinous exudates of bile ducts, were the most frequent gross lesions. Meanwhile, the histopathological examination showed hyperplasia, fibrous proliferation in the portal area and coagulative necrosis of hepatocytes with large numbers of inflammatory cell infiltration such as eosinophil, Kupffer cell and scattered lymphocytes in the area previously migrated by young flukes as well hepatocytes displayed a fatty change with dilated hepatic sinusoids. Furthermore, our findings show that the bile ducts have hyperplasia, which is associated with fibrous cholangitis and an abundance of inflammatory cells with accumulated bile pigment (hemosiderin) in the dilated bile ducts.