Many components in domestic sewage have been proved to have toxic effects, but it is far more enough to access the toxic effect of domestic sewage according to the known effects of the limited compounds. Due to the complexity of domestic sewage, it is difficult to identify the toxic effect of different components. Comparatively, it is more reliable to evaluate its toxic effect by using the whole sewage as a block in the toxic test. In the present study, domestic sewage was collected from a main sewage entrance of Lake Donghu and used in the experiment to investigate the toxic effects of domestic sewage. In order to test the potential toxic effect of domestic sewage, rare minnow( Grobiocypris rarus)was chosen as the experimental animal by the advantages of its small size, short sexual maturation period, easy breeding in the lab and its sensitivity to toxic compounds. Different exposure experiments at different life periods were carried out and the toxic effects were analyzed at morphological level and histological level. A 20-day short time exposure experiment during the early life stage from fertilized eggs showed that domestic sewage at. high concentration exerted acute toxic effect on rare minnow. The fertilized eggs could not hatch at the original concentration of the sewage, and there was a decreasing hatching rate and survival rate of fry and an increasing abnormality of fry as the concentration of the domestic sewage increased. In the 30-day exposure experiment during the gonad development period, micrographs of the liver samples collected from the exposed fish showed great toxic effect of the domestic sewage on fish liver cells. Cell nucleus of the exposed fish metamorphosed, mitochondria and endoplasmic reticulum became unclear, and lipid droplets appeared. Additionally, the gonad development of rare minnow was delayed when the concentration of the domestic sewage increased. In the four months full life cycle exposure experiment, the results showed that the domestic sewage delayed the growth and gonad development of rare minnow even at low concentration. Micrographs of liver samples collected from the exposed fish also showed great toxic effects of domestic sewage on the fish hepatocytes. Cell nucleus of the exposed fish metamorphosed,mitochondria and endoplasmic reticulum cannot be seen clearly, and many and large lipid droplets appeared. The results indicate that the original domestic sewage at the sewage entrance has acute toxic effect on the early life stage of fish. Directly discharging of the domestic sewage will affect the growth and gonad development of the fish near the sewage entrance.