Nerve conduction impairment in lead neuropathy has been empirically linked to altered nerve myo-inositol metabolism. In most cases of neuropathy, abnormal myo-inositol metabolism is associated with abnormal $Na^+/K^+$ATPase provides a potential mechanism to relate defects of the myo-inositol metabolism in the peripheral nerve treated with lead. Therefore, the effect of lead on the rat sciatic nerve $Na^+/K^+$ATPase and other ATPase of sciatic nerve was studied. ATPase activity was measured enzymatically in sciatic nerve homogenates from 2-wk lead treated neuropathy rats and age-mached controls administered myo-inositol. $Na^+/K^+$ATPase components were assessed by ouabain inhibition or the omission of sodium and potassium ions. Lead reduced 50% reduction in the $Na^+/K^+$ATPase activity in homogenates of sciatic nerve. The 50% reduction in the $Na^+/K^+$ ATPase activity was selectively prevented by myo-inositol treatment. This study suggests that the toxic mechanism of the lead on peripheral nerve may be through reduction in $Na^+/K^+$ATPase activity which has been linked to axonal transport slowing in the rat model of lead neuropathy, via direct changes by the perturbation of the intracelluar sodium or potasium level.