Microplastics (MPs) have received extensive attention as a new type of environmental pollutants with potential ecological risks. However, there are still few studies on the physiological stress response of aquatic organisms under the interaction of MPs and heavy metals. In this study, grass carp (Ctenopharyngodon idellus) were chosen as experimental fish and were exposed to 5 μm polystyrene microplastics (PS - MPs, 700 μg/L) and cadmium (Cd, 100 μg/L) individually or in combination. The results indicated that the presence of Cd didn't affect the accumulation of MPs in the intestines of grass carp. On the contrary, the concentration of Cd in the intestines of grass carp was higher in the MPs - Cd combined exposure group than in the Cd alone exposure group. Histological analysis revealed multiple abnormalities in the intestines after acute exposure, and the damage in the MPs - Cd combined exposure group was particularly severe. After 24 h of exposure, the expression of pro-inflammatory cytokines was significantly up-regulated in all exposed groups. However, after 48 h of exposure, the expression of inflammatory cytokines was significantly down-regulated, which may be related to intestinal damage. Our results deepen the significance of toxicological studies of MPs exposure, highlight their interaction with heavy metal toxicants, and provide important data for assessing the risk of MPs and heavy metals to grass carp.