Abstract: Micro-plastics are widely distributed pollutants in China's water environment. Sulfamethoxazole (SMZ) is frequently-used as antibiotics in aquaculture. However, the effect of micro-plastics on SMZ residues in tilapia muscle is unclear. The micro-plastics and sulfamethoxazole dosage in fishponds have been manipulated based on the ambient concentration, and the application of sulfonamides in aquaculture specified by SC/T 1084-2006. Three concentrations including:zero (NP), low (LP) and high (HP) micro-plastics in fishponds; and four doses of SMZzero (NS), low (LS), medium (MS) and high (HS) in forages were fabricated. For understanding the effect of micro-plastics on SMZ residues in tilapia (Oreochromis niloticus) muscle, an 8-weeks breeding experiment was conducted. Tilapia was fed in the first four weeks on a SMZ diet, followed by non SMZ diet for the next four weeks. SMZ content in fish meat was determined during the fourth, sixth and eighth weeks. The fourth week's results of SMZ residue in fish meat reveal that environmental micro-plastics could significantly reduce the residual value of SMZ in fish-meat. Single factor analysis of variance for the residual value of SMZ in fish meat at the 4^th, 6^th and 8^th weeks, reveal that after the 4^th week, all micro-plastic exposure groups at different SMZ dosage diets were significantly lower than those in the non-micro-plastic groups (P < 0.05), and there was no significant differences between the micro-plastic concentrations (P>0.05). After the 6^th week, only HP and NP groups with MS diet had significant differences (P < 0.05), and no significant difference was found in other SMZ feed groups of different micro-plastic treatments (P>0.05). Similarly, the results from the 8^th week, show that there was no significant difference in all groups fed on SMZ diet for the different micro-plastics treatments (P>0.05). In conclusion, the findings indicate that the effect of micro-plastics on sulfamethoxazole residues in fish-meat is limited by sulfamethoxazole dosage.