This study evaluated the histopathological changes in gills and liver of Prochilodus lineatus inhabiting the Salado River basin. Fish were collected in four different sampling stations. The histological lesions in the tissues were examined under light microscopy and evaluated with quantitative analyses. The morphometric analysis of the gills showed a significant shortening of secondary lamellae and a lower percentage of area for gas exchange in fish from station 1 (an urban area, located near the mouth of the Salado River) in comparison with fish gills from the reference site (station 4, a relatively pristine area). Moreover, a significantly higher area occupied with necrotic foci and the occurrence of an important inflammatory response were observed in fish liver of station 1 than the samples caught from other stations. Thus, histopathological evidences showed differences among sites, which could be related to different environmental conditions.