The primary function of white adipose tissues is to store excess energy. The current study aimed to investigate the roles of Gremlin 2 (Grem2), a glycoprotein in adipogenesis. Using polymerase chain reaction‑based microarrays, it was determined that Grem2 was markedly downregulated in adipose tissues from obese animals and humans. In addition, 3T3‑L1 cells were used to investigate the details of the mechanisms underlying the anti‑adipogenic effects of Grem2. Grem2 expression was markedly decreased upon the induction of adipocyte differentiation, as demonstrated by reverse transcription‑quantitative polymerase chain reaction and western blot analysis. Notably, Grem2 overexpression inhibited adipogenesis, while knockdown of Grem2 led to an increase in adipogenesis. At the molecular level, Grem2 promotes nuclear translocation of β‑catenin, an integral Wnt signaling component. Consistently, inhibition of Wnt/β‑catenin signaling using a retrovirus targeting the β‑catenin coding region attenuated the anti‑adipogenic effects of Grem2. Therefore, to the best of our knowledge, the current study shows for the first time that Grem2 may be an important regulator of adipocyte differentiation.