Molecular, cellular, and behavioral studies have shown that hypothyroidism impairs hippocampus-dependent learning and memory in adult rats. In these studies, spatial learning and memory were tested in the radial arm water maze (RAWM), which involved locating a hidden platform. In the present study, we investigated the effects of nicotine and hypothyroidism on the CaMKII pathway during learning and memory processes in both spatial and non-spatial memory forms. We used nicotine as a neuroprotective agent. Hypothyroidism was induced by thyroidectomy in adult rats. Rats were trained on the hidden platform (the RAWM for spatial learning and memory) and compared with age-matched rats that were trained on a clearly visible platform system (2 cm above water with no radial arms for non-spatial learning and memory). Nicotine (1 mg/kg twice/day) was administered subcutaneously for 4 weeks. Immediately after training, the protein levels of memory-related signaling molecules were determined in hippocampal area CA1. Western blot analysis revealed a significant increase in calcineurin levels and decreases in P-CaMKII, PKCγ, and calmodulin protein levels in area CA1 of the hippocampi of hypothyroid rats trained on both the visible and hidden platforms. Nicotine treatment normalizes these levels in hypothyroid rats trained on both the visible and hidden platforms. The results suggest that chronic nicotine treatment prevents hypothyroidism-induced suppression of the CaMKII pathway after spatial and non-spatial learning and memory.