The purpose of this study was to determine whether neutralization of rat interleukin-6 (IL-6) bioactivity increases the collateral blood supply from retrograde flow via the major middle cerebral artery branches after experimental middle cerebral artery occlusion in the rat. Seventy rats were randomly allocated to four main groups: Group I (n = 10) consisted of normal controls, Group II (n = 20) underwent craniectomy only; Group III (n = 20) was subjected to middle cerebral artery occlusion; and Group IV (in = 20) underwent middle cerebral artery occlusion and treatment with anti-rat IL-6 antibody. Half of the rats from each of Groups II, III and IV were killed at 24 h and the other half at 72 h after craniectomy alone or occlusion. A single dose of antibody did not affect middle cerebral artery caliber, but administration of three doses resulted in a significant increase in the diameter of middle cerebral artery compared to the findings in the corresponding occlusion-only groups. The results suggest that neutralization of rat IL-6 bioactivity in long-term recovery increases the collateral blood supply from retrograde flow via cortical anastomoses after experimental arterial occlusion in the rat brain.