With the multifaceted activities of nucleotides, there is a history of safe consumption of dietary nucleotides (NTs) in the human diet. This study investigated the multigenerations cumulative toxicity on rats' development after weaning. Weaning rats (F0) were fed with NTs at the dosage of 0.01, 0.04, 0.16, 0.64, and 1.28% (wt/wt) for 90 days and then mated for 1:1 pattern. The offspring was F1. F1 rats were fed with NTs for 90 days after weaning. Afterwards, F1 go on to the second reproductive part. We repeated the above process, until F3 rats were born. We observed the weight, food consumption in the whole experiment, and detected the blood indicators and organ pathology at the terminal. No abnormal reaction, behavior disorder, and organ pathology related to toxic symptom were observed in NTs-treated groups. Weight gain and diet utilization ratio of males in each NTs group had significant increase after weaning (p < 0.05). With the exception of decrease in uric acid (p < 0.05) of NTs male, there were no differences between the control and NTs groups in blood indicators. NTs could promote early growth and development of rats after weaning, especially in males.