Enhancing nitrogen use efficiency is one of the most important strategies for improving productivity in agriculture and reducing risk of environmental pollutions in sustainable agriculture. In order to study the effects of different levels of organic manure and chemical fertilizer on nitrogen uptake efficiency (NupE), nitrogen utilization efficiency (NutE) and nitrogen use efficiency (NUE) of isabgol (Plantago ovata Forsk.), a field experiment was performed based on a randomized complete block design with three replications at the Agricultural Research Station, College of Agriculture, Ferdowsi University of Mashhad, during growing season of 2011-2012. Treatments included three levels of nitrogen fertilizer (25, 50 and 75 kg.ha-1), three levels of cow manure (5, 10 and 15 t.ha-1), three levels of vermicompost (2, 4 and 6 t.ha-1) and control. Seed yield, biological yield and nitrogen content of biomass of isabgol were measured and then NupE, NutE and NUE based on seed yield and biological yield were calculated accordingly. The results showed that the different fertilizers had significant effects on all studied traits of isabgol. The highest seed yield and biological yield of isabgol were observed in 6 t.ha-1 vermicopmpost with 98.2 and 54.8 g.m-2, respectively. By increasing fertilizer rate, nitrogen percentage and content of biomass were increased. The maximum NutE and NupE were achieved in control plots. Also, the highest and the lowest NupE of isabgol were obtained in 5 t.ha-1 cow manure and 75 kg.ha-1 N with 8.9 and 7.0 gN per g-1 Ns, respectively. Organic manures improved NupE and NUE more than chemical fertilizer. So, organic manure application enhanced yield, NupE and NUE of isabgol compared to chemical fertilizer. So, it seems that organic input application could be considered as a sustainable approach for improving growth and yield of medicinal plants such as isabgol in agroecosystems that will increase nitrogen efficiency and reduce environmental pollutions due to slow release of nutrients.