Abstract Objectives The role of interleukin (IL)-1β in intense acute swimming-induced muscle mechanical hyperalgesia was investigated in mice. Methods Untrained mice were submitted to one session of intense acute swimming for 120 min or were submitted to sham conditions (30 s exposure to water), and muscle mechanical hyperalgesia (before and 6–48 h after swimming session), IL-1β production (skeletal muscle and spinal cord), myeloperoxidase activity, reduced glutathione (GSH) levels (skeletal muscle and spinal cord), and cortisol, glucose, lactate and creatine kinase (CK) levels (plasma) were analysed. Key findings Intense acute swimming-induced muscle mechanical hyperalgesia was dose-dependently inhibited by IL-1ra treatment. IL-1β levels were increased in soleus, but not gastrocnemius muscle and spinal cord 2 and 4 h after the session, respectively. Intense acute swimming-induced increase of myeloperoxidase activity and reduced GSH levels in soleus muscle were reversed by IL-1ra treatment. In the spinal cord, exercise induced an increase of GSH levels, which was reduced by IL-1ra. Finally, IL-1ra treatment reduced plasma levels of CK, an indicator of myocyte damage. Conclusions IL-1β mediates intense acute swimming-induced muscle mechanical hyperalgesia by peripheral (soleus muscle) and spinal cord integrative mechanisms and could be considered a potential target to treat exercise-induced muscle pain.