Ecotoxicological studies that use histological techniques enjoy descriptive approach in explaining the damages to tissues. In the present study, a rank-based estimation for linear models was used to examine significant difference between levels of cypermethrin on histological changes of the liver in Aphanius sophiae. The toxicity of cypermethrin associated with certain environmental factors such as salinity and feeding frequency was studied in the Sophiae toothed carp (A. sophiae). Specimens were exposed to concentration of 0.02 μg L-1 cypermethrin, two levels of salinity (0 and 14 ppt) and feeding frequencies (two times a day and one time every three days) under laboratory conditions. After the end of 14 days period of the experiment, the liver tissues were removed and histological sections prepared. The results revealed that liver tissues alter significantly with the changes in salinity and diet frequency. The results also showed that sensitivity to cypermethrin increased with decreasing salinity and increasing feeding frequency. The results suggested using A. sophiae as an indicator for cypermethrin assessment in aquatic ecosystems and appropriateness of rank-based estimation for linear models, to evaluate the effect of toxins on histopathological alternations