Aim To investigate the expression and function of transmembrane protein 16A (TMEM16A) after acute myocardial infarction (AMI) in the left ventricular fibroblasts of minipig. Methods The AMI models were induced by ferric chloride (FeCl₃)-induced thrombosis in the left anterior descending coronary artery (LAD). Four hours after AMI, the infarction models were evaluated by enzymology and echocardiography. And, twenty-four hours after AMI, the TMEM16A mRNA level was measured by quantitative real-time PCR (qRT-PCR) in minipig ventricular fibroblasts; the changes of current intensity were determined by patch-clamp. Results Compared with the sham groups, the concentration of cardiac troponin I (cTnI), creatine kinase isoenzyme (CK-MB) and myoglobin (MYO) were significantly increased in the AMI model groups, and the left ventricular ejection fraction (LVEF) had a significant decrease ((53.4±1.9)%, P<0.05). The gene expression level of TMEM16A was dramatically upregulated, and the current intensity was also significantly enhanced (P<0.05). The amplitude of current was (1.58±0.67) pA/pF, (3.69±1.26) pA/pF, (7.60±2.14) pA/pF, (12.94±2.38) pA/pF, (22.19±2.61) pA/pF at stimulation voltages of +20, +40, +60, +80 and +100 mV, respectively. Conclusions These results suggested that TMEM16A was expressed in ventricular fibroblast cells of minipig. Moreover, the TMEM16A expression level was up-regulated after AMI; and calcium-actived chloride current (ICl,Ca) was enhanced by influencing calcium-activated chloride channels (CaCC).