Introduction: Olanzapine is an atypical antipsychotic prescribed usually for treatment of psychiatric disorders as schizophrenia. It has been widely documented to induce pancreatitis and type 2 diabetes mellitus. Granulocyte colony stimulating factor (G-CSF) is an approved drug for treatment of leucopenia and for mobilization of haemopoietic stem cells from bone marrow towards peripheral circulation. Umbelliferon is a natural plant product that has multiple pharmacological characteristics, including anti-inflammatory, antioxidant, anti-apoptotic and anti-diabetic actions. Aim of the Work: This research intended to compare the potential therapeutic benefits of umbelliferon and G-CSF on induced pancreatic injury. Materials and Methods: We utilized forty-eight adult male albino rats that were subdivided into 4 groups; control group, olanzapine group, G-CSF treated group and Umbelliferon treated group. All animals were sacrificed at the end of the experiment and then tissue and serum were gathered for a biochemical analysis. Histological sections from each group were taken and examined under the light and electron microscopes. Results were subjected to morphometrical and statistical studies. Results: The histological and biochemical results showed different pathological changes of the pancreatic tissue in olanzapine group as distorted acini, thickened septa and congested blood vessels. Also elevated serum amylase and oxidative stress markers as MDA and SOD was shown in the olanzapine group. The GCSF-treated group showed a histological and biochemical improvement, however the structural and biochemical improvement in the umbelliferon group was more than that shown in the G-CSF group. Conclusions: Finally, we concluded that, umbelliferon administration caused a marked ameliorative effect on olanzapine induced pancreatic injury as a comparable to G-CSF treatment