The Wnt/β-catenin signaling pathway has been widely associated to the reestablishment of anteroposterior body polarities in the embryonic development and regeneration in animals. For instance, in annelids, cellular proliferation, wound healing, and blastema development can be affected when this pathway is disrupted. However, very little is known about the genetic regulatory processes involved in these anomalies. Here, we investigate the morphological effects of 1-azakenpaullone, a pharmacological inhibitor of GSK3β that is supposed to over-activate the Wnt/β-catenin pathway, during the anterior and posterior regeneration of the annelid Syllis malaquini. The results showed that high concentrations of 1-azakenpaullone affect the stages of blastema differentiation and resegmentation. Therefore, GSK3β-associated gene regulatory networks are candidate to investigate the genetic mechanisms involved in the regular course of S. malaquini regeneration.