This study evaluates the effects of substituting fishmeal with earthworm meal on the growth, muscle composition, and biochemistry index in serum and immunity performance in the loach with an average initial body weight of (3.86±0.23) g. Five experimental diets with the same nitrogen and energy content were formulated to replace fishmeal using 0 (as the control group), 25%, 50%, 75% and 100% of earthworm meal. The experimental fish were fed the alternative diets in net cages for 10 weeks. Results showed that dietary fishmeal replacement with earthworm meal had no significant effect on the survival rate of loach. The feed conversion ration (FCR) and weight gain rate (WGR) increased (<0.05), and the condition factor (CF) and hepatosomatic index (HSI) decreased (<0.05), as levels of substitution rose to the maximum. There was no significant difference in splenic index (SI) or specific growth rate (SGR) in any of the groups. The content of fat in the flesh at levels of 75% and 100% replacement was significantly higher compared with the control group (<0.05); and the content of flesh crude protein and moisture in the 100% replacement diet was significantly lower than in the control group (<0.05). As the content of earthworm meal rose, the content of Arg, Cys and Asp in flesh protein also increased (>0.05), but that of Pro, His, Met, Thr and Phe in flesh protein decreased significantly (>0.05) in the vitality of alanine aminotransferase (ALT), lipase (LPS) and amylase (AMS), or in the content of high density lipoprotein cholesterol (HDL-C)in the serum of treatment groups. As the fishmeal content dropped, triglyceride (TG) and total cholesterol (TCHO) increased (<0.05), but aspartate aminotransferase (AST) decreased significantly (<0.05). As levels of substitution increased up to the maximum, the vitality of catalase, glutathion peroxidase (GSH-Px) and lysozyme (LZM) in the hepatopancreas decreased; the content of malonaldehyde (MDA) and the vitality of alkaline phosphatase (AKP) in the hepatopancreas increased; and morbidity and death rate after bacterium Aeromonas hydrophila challenge also increased. There was no significant difference in the vitality of total superoxide dismutase (TSOD) and total antioxidant capacity in the hepatopancreas of treatment groups (>0.05). This study demonstrated that replacing 22% of the fishmeal in the diet by earthworm meal had no significant effect on growth and survival, and could promote muscle composition. It could also effectively protect the hepatopancreas from damage and peroxidation by reactive oxygen; however, it would significantly inhibit loach immunity performance.