We have observed that, after myocardial infarction (MI), rats display apoptosis in the limbic system that can be prevented by pentoxifylline (PTX), a proinflammatory cytokine inhibitor. We have hypothesized that reduction of apoptosis in the limbic system can attenuate the depressive behaviour occurring post-MI. The present study was, therefore, designed to assess the outcome of PTX on depressive behaviour manifesting after MI. Myocardial ischaemia, induced for 40 min in male Sprague-Dawley rats, was followed by reperfusion (MI groups). Sham groups were subjected to the same protocol without occlusion. PTX (10 mg/kg/day) or saline was administered intraperitoneally 15 min before ischaemia, and then every day until sacrifice. Two weeks after ischaemia, depression was evaluated by the forced swim test and the sucrose preference test. At the end of the experiment, the animals were sacrificed, and myocardial infarct size was examined along with plasma IL-1β concentrations. MI rats drank less sucrose in the sucrose preference test and were more immobile in the forced swim test than the sham controls. PTX reversed these behaviours in the MI group to a level similar to that in the untreated sham group, without affecting infarct size. PTX reduced plasma IL-1β concentrations in both sham and MI rats. We conclude that PTX administration significantly reverses the depressive-like behaviour seen after MI in rats.