Aims: This study aims to simulate dissolved oxygen of Zayandehrood river from regulating dam to Polle-Kalleh bridge using MIKE11 software that is a hydrodynamics and water quality model. Materials and Methods: During 5 months the samples were taken from four hydrometric stations and water quality parameters such as dissolved oxygen, pH, BOD (1 day, 3 days, 5 days, and 7 days), NH 4 , NO 3 - phosphate (PO4 3- ), and temperature were measured. Morphological and hydrological data were provided and introduced into the model. The model was calibrated and its accuracy was investigated. Results: The results indicated that concentration of PO4 3- , BOD5 , COD, NH 4 , and NO3 - exceeded surface water standards from regulating dam to Pole-Kalleh bridge. The results of the prediction for the next 25 years indicated that due to growth of population and industries along the river, concentration of some pollutants will be increased. Conclusions: The results indicated that although the current DO level is suitable for aquatic environment, this is not adequate for fish reproduction and migration. Prediction of the river water quality parameters for the future conditions showed that discharge of urban and rural wastewater to river should be avoided. In situations where release of effluent into the river is inevitable, nitrification process should be added to wastewater treatment processes.