Lysine-rich rice (LR) is a transgenic rice produced by fusion protein expressed genes into the germline of rice seeds. Compositional analysis of LR showed that the absolute concentration of lysine was significantly higher as compared to a near-isogenic non-transgenic rice. Lysine is believed to be the first limiting essential amino acid in rice, it is important to improve lysine content on rice nutritional quality. Here we report the results of a three generation study comparing the outcome in rats fed the transgenic rice to those fed conventional, near-isogenic rice or a control diet. In the study, both clinical performance variables and pathological responses such as body weight, food consumption, reproductive data, hematological parameters, serum chemistry and relative organ weights were examined respectively. It was evident that there were no adverse effects observed in rats that were fed transgenic rice compared with non-transgenic rice. There were significant differences in some hematology, serum chemistry parameters and relative organ weights in rats consuming the transgenic rice diet or non-transgenic rice diet compared with the control diet, but no macroscopic or histological adverse effects were observed. So the results from this study demonstrate that LR rice is as safe as near-isogenic non-transgenic rice.