Recent theories of economic growth treat commercially oriented innovation in response to economic incentives, as a major engine of technological progress and productive growth. In this view, innovation feeds on knowledge arising from cumulative research and development (R&D) experience on one hand, and it contributes to this stock of knowledge on the other hand. Consequently, an economy's level of productivity depends on its cumulative R&D effort and on its effective stock of knowledge, with the two being interrelated. In a world with FDI and international trade in goods, a country's productivity depends on the R&D of its trade partners as well as its own.The aim of this study is to assess the role of domestic R&D expenditures and foreign R&D expenditures (through the foreign trade and FDI). Human capital and macroeconomic variables on Total Factor Productivity (TFP) in Iran's economy. We apply Johansen cointegration methodology and 015 in the estimation during the period between 1338-1382.The findings show that domestic R&D capital stock, foreign R&D capital stock(through the foreign trade and FDI), Human capital, capital intensity, ratio of exports of GDP, external reserves, real exchange, rate inflation rate and Dummy variables have important effects on Total Factor Productivity. Our estimates suggest that the coefficient of domestic and foreign R&D capital stock, ratio of exports of GDP, and Dummy variables on TFP, is larger than the coefficient variables. Our estimates also show that the coefficient variable inflation rate and Dummy variables on TFP is negative.In addition, we discussed various shocks and their immediate effects on different variables through application of impulse response and variance decomposition, and showed the effect of changes of variable.