Cardiac hypertrophy is a common pathological change accompanying cardiovascular disease. Recently, some evidence indicated thatcalcium-sensing receptor (CaSR) expressed in the cardiovascular tissue. However, the functional involvement of CaSR in cardiac hypertrophyremains unclear. Previous studies have shown that CaSR caused accumulation of inositol phosphate to increase the release ofintracellular calcium. Moreover, Ca2+-dependent phosphatase calcineurin (CaN) played a vital role in the development of cardiac hypertrophy.Therefore, we investigated the expression of CaSR in cardiac hypertrophy-induced by angiotensin II (AngII) and the effects ofCaSR activated by GdCl3 on the related signaling transduction pathways. The results showed that AngII induced cardiac hypertrophyand up-regulated the expression of CaSR, meanwhile increased the intracellular calcium concentration ([Ca2+]i) and activated CaNhypertrophic signaling pathway. Compared with AngII alone, the above changes were further obvious when adding GdCl3. But theeffects of GdCl3 on the cardiac hypertrophy were attenuated by CsA, a specific inhibitor of CaN. In conclusion, these results suggestthat CaSR is involved in cardiac hypertrophy-induced by AngII through CaN pathway in cultured neonatal rat cardiomyocytes.