To study the effect of various fertilizer doses and microbial inoculants in soybean – safflower cropping system on soil properties, yield, soil enzymes and nutrient uptake. The field experiments were conducted during kharif and rabi seasons of 2009-10 and 2010-11 at Research Farm of Department of Soil Science and Agricultural Chemistry, Marathwada Agricultural University, Parbhani. The experimental soil was clay with pH 8.3. It was moderately fertile, being low in organic carbon, available nitrogen, medium in phosphorus with high content of potassium. Treatments comprised of three fertility levels (100% RDF, 75% RDF and control) and four treatments of bioinoculants (N-fixers, PSB, N-fixers + PSB and control). The experiment was laid out in factorial randomized block design with four replications. Results from the study showed the maximum grain and straw yield, soil nutrient status (OC, N, P, K, S, Zn and Fe) and total nutrients uptake (N, P, K, S) was improved with 100% RDF and inoculation with N-fixers + PSB. An application of 75% RDF significantly increased soil microbial population (Bacteria, actinomycetes and fungi) and soil enzymes activity (Nitrate reductase activity, alkaline and acid phosphatases activity) and dual inoculation also improved above parameters in soybean-safflower cropping system.