Abstract: It has been shown that the ATP competitive small molecule inhibitor SP600125 can efficiently induce fish cell polyploidization in vitro. In this study, we used SP600125 to directly incubate the fertilized eggs of crucian carp to obtain the possibility of polyploid fish, and found that SP600125 caused partial embryo ploidy, significantly affected the embryonic development and led to high mortality of embryos. SP600125 also induced a large number of malformed fry after treating fertilized eggs, mainly skeletal dysplasia such as spinal curvature and tail loss. The skeletal malformation caused by SP600125 was further validated. Real-time PCR indicated that SP600125 significantly induced mRNA levels of skeletal development-related genes, such as smad6, stat1, lef1, bmp2 and twist1 in vivo (fertilized eggs and fry) or in vitro (cultured caudal fin cells). These results clearly help to develop a potential mode of fish polyploidy induced by SP600125.