Erythromycin (ERM) is a macrolide antibiotic and is widely used to prevent and treat respiratory tract infections, acute pelvic inflammatory disease, amygdalitis, skin infection, and so on. ERM is of high concern due to their abundant occurrence in various environmental media and their toxic risk to aquatic organisms. However, knowledge on the molecular mechanisms of ERM toxicity and its effects on reproduction and growing development output remain scarce. In order to reveal the ecotoxicological effects of ERM on aquatic organisms, acute toxicity and chronic effects of reproduction, growth and development were conducted on the standard model organism Daphnia magna. The results of acute toxicity showed that the LC₅₀ of ERM for the 48 h and 96 h were 315.41 mg/L and 163.08 mg/L, respectively, belonging to low toxicity under the rules for classification and labelling of chemicals. In this experiment, 0.01‰ (2 μg/L) and 1‰ (200 μg/L) of 96 h-LC₅₀ were selected as the exposure concentrations for ERM chronic toxicity test. During the chronic toxicity test of 21 days, the ecological behavior indexes related to the growth, development and reproduction of Daphnia magna were recorded, and the population growth indexes were calculated. At the end of the 21-day exposure, the enzyme activities of antioxidant system and neurological system and the expression of genes related to growth, reproduction and metabolism of Daphnia magna were investigated. Following ERM exposure at concentrations of 2 μg/L and 200 μg/L, phenotypic traits including growing development (body length, heart rate, thoracic limb activity) and fecundity (number of offspring, number of offspring per brood per female, intrinsic rate of increase) were obviously increased, and swimming activity (swimming trajectory and swimming speed) were clearly reduced. Lipid peroxidation malondialdehyde contents were significantly increased at day of 21, the antioxidant enzymes (superoxide dismutase and glutathione S-transferase) and neurotoxic enzymes (acetylcholinesterase) exhibited a trend towards inhibition at higher concentration, suggesting that ERM could result in oxidative damage and nerve conduction disorder. Upregulation of genes involved in reproductive and developmental process, including vg1, vtg2, jhe, ecrb and cyp314 were observed, meanwhile the genes related to lipid metabolism and detoxification (hr96 and P-gp) were clearly inhibited, which regulates the phenotypic traits and corresponding protein levels of Daphnia magna. The alterations in developmental and reproductive system as well as the disturbed antioxidant system and neurological system of zooplankton for ERM provides basic data support for revealing the effects of antibiotics on aquatic organism population stability and ecosystem security.