Borage (Borago officinalis L.) is a valuable medicinal plant and its production to meet the needs of the pharmaceutical industry has a high value. The objectives of this work were to evaluate water quality and different fertilizer systems on some physiological and biochemical characteristics of borage. The experiment was conducted as a split-plot arrangement based on compelet block design with three replications in 2012 at the research farm of Zabol University, Zabol, south Iran. The treatments were two irrigation sources: irrigation with fresh and saline water as main-plot, and four fertilization system: application of NPK at 80:40:30 kg ha-1, 40 ton of manure ha-1, NPK at 40:20:15 kg ha-1 plus 20 ton of manure ha-1 and no soil fertility as sub-plot. Salt irrigation water significantly increased antioxidant enzymes, carbohydrates and proline contents. The low quality of irrigation water reduces plant protein, chlorophyll fluorescence and moisture content, however mucilage content did not influence. Application of fertilization significantly increased all studied traits compared with the control except chlorophyll fluorescence. Combination of organic and inorganic fertilizer was more effective than sole application. Interaction of water quality by fertilization was significant only on ascorbate peroxidase. These results suggested that although irrigation with saline water decreased quantitatve and qualitative characteristics of borage, however, replacement part of chemical fertilizers with organic fertilizers can reduce environmental pollution.