A feeding trial was performed to investigate the effects of the partial replacement of fish meal with distiller’s dried grains with solubles (DDGS) on growth, feed assessment, economic assessment, digestibility of diets, as well as liver and intestinal histology of rainbow trout (Oncorhynchus mykiss). Four isonitrogenous and isocaloric diets were prepared using DDGS in rates of 0%, 10%, 20% and 30% (Control, DDGS10, DDGS20, and DDGS30, respectively) instead of reducing the fish meal content. Triplicate groups of 25 rainbow trout (mean initial weight 19.88±0.02 g) were fed with the diets for 84 days. The results revealed that dietary DDGS30 had the highest final weight and specific growth rate. Feed conversion and protein efficiency rates were similar among the dietary treatments. Economic conversion ratio was reduced depending on DDGS increase in diet that resulted in an increased economic profit index. The apparent digestibility of the diets did not differ significantly among treatments. There were no significant differences in the diameter of hepatocyte nuclei but there was a detected amount of vacuolization in the hepatocyte cytoplasm of fish fed the dietary DDGS20 and DDGS30 diets. Distal intestine histomorphometric parameters were unaffected by dietary treatments, however, increased lamina propria width was observed as the rate of DDGS increased in diets. These results indicate that DDGS can be added to rainbow trout diets by up to 30% without negatively affecting growth performance, diet digestibility, as well as the histology of the liver and intestine.