Acid-soluble (ASC) and pepsin-soluble (PSC) collagens were isolated from tilapia skin and were characterized as type I collagen. The T-d (denaturation temperature) of ASC and PSC was 26.80 and 28.20 degrees C, respectively. CD (circular dichroism) and FTIR (Fourier transform infrared) spectra of ASC and PSC were slightly different, which confirmed that limited digestion by pepsin disrupted the triple helical structure of collagen. The microstructure depicted a homogeneous, compact, fibrillary, and multilayered sheet like structure. Notably, no toxicologically effect (survival rate, behavioral activity, respiratory illness, abdominal irritation, eye lid and prolapse) was observed in collagen treated mice. The body weight of the ASC-treated mice (36.1-38.6 g) was significantly higher than that of the PSC-treated mice (32.9-36.7 g). In Vitro absorption properties revealed that type I collagen hydrolysates with molecular weights (MWs) ranging from 100 to 12 kDa were effectively absorbed by intestinal villi. Taken together, these results suggest that tilapia type I collagen at the concentrations of 25 and 50 mg/kg bw has no higher risk of chronic toxic effects in mice. Therefore, it was concluded that the administration of tilapia type I collagen had low toxicity and confirmed the in vivo biocompatibility for its wide application in the biomedical industries. (C) 2016 Elsevier Ltd. All rights reserved.