The purpose of this article is to examine the influence of the following key macroeconomic indicators: GDP, inflation rate, money supply, interest rate and balance of payments on exchange rate of the Romanian leu against the most important currencies (EUR, USD) during 2000-2010 period. The main findings of our study are: it is an inverse relationship between exchange rate EUR/RON, Gross Domestic Product, respectively money supply and a direct relationship between exchange rate EUR/RON, inflation and interest rate. We can not validate the correlation between exchange rate and Balance of payment, because the test statistic is not significant.