We investigated the myocardial thioredoxin‐1 and hydrogen peroxide concentrations and their association with some prosurvival and pro‐apoptotic proteins, during the transition from myocardial infarction (MI) to heart failure in rats. Male Wistar rats were divided into the following six groups: three sham‐operated groups and three MI groups, each at at 2, 7 and 28 days postsurgery. Cardiac function was analysed by echocardiography; the concentration of H₂O₂ and the ratio of reduced to oxidized glutathione were measured spectrophotometrically, while the myocardial immunocontent of thioredoxin‐1, angiotensin II, angiotensin II type 1 and type 2 receptors, p‐JNK/JNK, p‐ERK/ERK, p‐Akt/Akt, p‐mTOR/mTOR and p‐GSK3β/GSK3β was evaluated by Western blot. Our results show that thioredoxin‐1 appears to make an important contribution to the reduced H₂O₂ concentration. It was associated with lower JNK expression in the early period post‐MI (2 days). However, thioredoxin‐1 decreased, while renin–angiotensin system markers and levels of H₂O₂ increased, over 28 days post‐MI, in parallel with some signalling proteins involved in maladaptative cardiac remodelling and ventricular dysfunction. These findings provide insight into the time course profile of endogenous antioxidant adaptation to ischaemic injury, which may be useful for the design of therapeutical strategies targeting oxidative stress post‐MI.