The blood brain barrier (BBB) maintains brain homeostasis by limiting entry of substances to the central nervous system (CNS) through interaction of transmembrane and intracellular proteins making up endothelial cell tight junctions (TJs). Recently it has been shown that the BBB can be modulated by disease pathologies, including inflammatory pain. This study examines the effects of chronic, inflammatory pain on the functional and molecular integrity of the BBB. Inflammatory pain was induced by injection of Complete Freunds Adjuvant (CFA) into the right plantar hind paw in female Sprague-Dawley rats under halothane anesthesia; control animals were injected with saline. Edema and hyperalgesia were assessed by plesmythmography and infrared (IR) paw withdrawal latency. Seventy-two hours post-injection, significant edema formation and hyperalgesia were noted in the CFA-treated rats. Examination of permeability of the BBB by in situ perfusion of [¹⁴C]-sucrose, under pentobarbital anesthesia, demonstrated that CFA treatment significantly increased sucrose brain uptake. Western blot analysis of BBB TJ proteins showed no change in expression of zonula occludens-1 (an accessory protein) or actin (a cytoskeletal protein) with CFA treatment. Expression of the transmembrane TJ proteins occludin, claudin-3 and claudin-5 significantly changed with CFA treatment, with a 60% decrease in occludin expression, a 450% increase in claudin-3 and a 615% increase in claudin-5. This study demonstrates that during chronic inflammatory pain alterations in BBB function are associated with changes in specific transmembrane TJ proteins.