An earlier study of ours has shown that blocking FGF2 signaling curtails the onset and progression of tail regeneration in fish. The current study was envisaged to understand the mechanistic reasons behind the compromised tail fin regeneration in response to SU5402 treatment in fish Poecilia latipinna. Results showed that the FGF receptor antagonist significantly reduced the DNA, RNA and protein turnover during the wound healing and blastema stages of regeneration. Moreover, striking alterations in the protein profile was also noticed during this period of regeneration in the treated group of fishes. However, upon reaching differentiation stage of epimorphosis the studied parameters by and large were found comparable between the control and treated animals. Therefore, it could be inferred that the FGF2 signalling is inevitable for the successful attainment of initial events of regeneration during fish fin regeneration.