Background and Aims Apoptosis of acinar cells plays a crucial role in the inflammatory response and progression of acute pancreatitis (AP). A better understanding of the apoptotic mechanisms and related pathways in acinar cells can provide new insights for AP-specific therapies. This study was conducted to investigate the expressions of the zinc finger protein gene ZMYM2 transcribed circular RNA (circZMYM2), microRNA-29a (miR-29a), and p53 upregulated modulator of apoptosis (PUMA) in AP and their potential relationships.Methods Rat pancreatic acinar cells AR42J were induced to form an in vitro model of AP using cerulein (AP group) or were transfected with pcDNA3.1-si-ZMYM2 to knock down circZMYM2 expression before cerulein induction (si-circZMYM2 group), using untreated AR42J cells as a control group. After 3 h, the amylase level was determined by ELISA assay, the cell viability was assessed by CCK-8 assay, the apoptosis was measured by flow cytometry and TUNEL assay, and the PUMA protein expression was examined by Western blot analysis, and the circZMYM2 and miR-29a expression levels were detected by qRT-PCR method.Results Compared to the control group, the AP group and si-circZMYM2 group showed significantly increased amylase levels, decreased cell viability, increased apoptosis rates or apoptotic cell numbers, and elevated PUMA protein expression (all P<0.05). However, the changes in the above indicators were significantly less pronounced in the si-circZMYM2 group than those in the AP group (all P<0.05). The expression level of circZMYM2 was significantly increased in the AP group and significantly decreased in the si-circZMYM2 group, while the expression level of miR-29a was significantly downregulated in the AP group and significantly upregulated in the si-circZMYM2 group compared to the control group (all P<0.05).Conclusion The expression of circZMYM2 in acinar cells during AP is upregulated, and it may probably inhibit miR-29a expression through endogenous competition, thereby upregulate PUMA expression level and then promote acinar cell apoptosis and AP progression.