Background/Aims: Pregnancy is characterized by vasodilatation and increased glomerular filtration rate (GFR), despite overstimulation of the renin angiotensin system (RAS). The mesangial cells (MCs) influences GFR and when cultured from pregnant rats displays refractoriness to Ang II. We evaluated the role of relaxin (RLX) and its receptor (RXFP1), nitric oxide (NO) and the AT2 receptor in this response. Methods: MCs cultured from kidneys of virgin (V) and pregnant (P) Wistar rats were treated with RLX or AT2 receptor blocker PD123319 or NO synthase inhibitor L-NAME. After 24 hr, intracellular calcium concentration ([Ca]i) was recorded before and after the addition of Ang II. Results: MCs from V group expressed AT2, RLX and RXFP1, whose levels were increased in P cells. Ang II induced a 150% increase in [Ca] i in the V cells and 85% (p<0.05) in the P cells. V cells treated with RLX displayed a similar response to that observed in P cells, suggesting that RLX can modulate the reactivity of the MCs to Ang II. L-NAME and PD123319 did not interfere in this response. Conclusion: Results suggest that RLX is a mediator of the refractoriness of the MCs to Ang II during pregnancy.