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Objective(s): Recently, applications of MnO2 nanoparticles and microparticles in industry, pharmacology, and medicine have considerably expanded. Mn distribution and clearance from brain and spinal cord tissue compared with muscle tissue of rats after single subcutaneous injection of nanoparticles and microparticle of MnO2 . Pain sensory threshold of rat was evaluated as neurologic consequence of the particles on CNS activity of rats.   Materials and Methods: Rats divided to control and two experimental groups. Each experimental group received a single subcutaneous injection of MnO2 nano- and microparticles, respectively. Acute pain thresholds of rats were evaluated by tail immersion method and its weight gain was recorded during these weeks. Samples taken from brain, spinal cord and muscle tissues of rats, once every 2 week for 8 weeks. The tissue Mn level was measured by inductively coupled plasma-mass spectrometry method. Results: Both particles size passed from blood barriers. Unlike brain tissue, manganese completely cleared from spinal tissue after 8 weeks in both groups. Clearance of Mn from muscle tissue is not complete in both of the groups. Weight gain of rats in both groups was slower than control rats. In microparticle group, rats showed progressive analgesia (p