The purpose of the present study was to evaluate the effectiveness of fish oil in preventing tissue pathologies associated with monocrotaline (MCT) toxicity. Twenty-four weanling rats were randomly assigned to one of two groups: (1) 12 to a group fed a diet containing 15% (w/w) corn oil (control) and (2) 12 to a group fed a diet containing fish oil (13%) and corn oil (2%) as the source of fat. Rats were fed for 4 weeks prior to MCT treatment. Six rats in each group were subcutaneously injected with MCT and six injected with its vehicle (water) and all were continued on their respective diets. All rats were sacrificed 3 weeks after injection. In rats receiving MCT, we observed severe interstitial pneumonia, septal fibrosis, vasculitis with virtual obliteration of the lumen of the small arteries and arterioles, right ventricular hypertrophy (RVH), and hepatomegaly and hepatocyte vacuole formation. Dietary fish oil significantly reduced septal fibrosis and development of pneumonia. There was a slight, but statistically insignificant decrease in vasculitis and fish oil did not prevent RVH (pulmonary hypertension). In addition, fish oil effectively protected the MCT-treated rats from development of hepatocyte vacuoles (steatosis), hepatic inflammation and vasculitis, increased presence of fibroblasts and collagen deposition in the centrilobular and, to a lesser extent, in the periportal spaces. These results suggest that lung parenchymal inflammation can be attenuated without altering the course of development of pulmonary hypertension in the MCT model. These results also indicate that fish oil protects against inflammation and fibrosis in the lung and liver, and against hepatocyte vacuole formation in MCT-treated rats.