There are provided an endoscope system capable of narrowing down the range to index values that are to be noticed upon diagnosis and presenting the index values even in a case where a plurality of index values are used and an operation method of an endoscope system.An image processing unit (60) includes an image acquisition unit (70), an extraction unit (72), an index value calculation unit (74), a determination unit (76), a color information setting unit (78), and an image generation unit (80). The image acquisition unit (70) acquires an image captured by an endoscope (12). The extraction unit (72) extracts a blood vessel of an observation target. The index value calculation unit (74) calculates a plurality of blood vessel index values based on the blood vessel. The determination unit (76) determines whether each of the plurality of blood vessel index values is a normal value or an abnormal value. The color information setting unit (78) sets color information for an abnormal index value, which is the blood vessel index value determined to be the abnormal value by the determination unit (76), or sets color information for a normal index value, which is the blood vessel index value determined to be the normal value by the determination unit (76). The image generation unit (80) generates an emphasized image, in which the blood vessel is emphasized, based on the color information.