Is there biological sex difference in human? It is said that men have good spatial recognition ability or are good at math and women have good empathy ability. There are many papers about sex differences. Some papers say there are sex differences and some papers say not. I think there are sex differences between men and women. But it includes cultural effect. Are there "biological" sex difference in human? No one knows the right answer because we cannot remove cultural effect. But we have some ways to approach this topic. First, to use animals. We can raise animals in environment completely separated from culture. Mice has sex differences in some behavior such as coordination, anxiety-like behavior and spatial and non-spatial task performance. Second, to compare difference culture. Interestingly, difference in spatial recognition ability is more appear in countries that have big gender gap. Both methods have problems. Animal is different from human and the definition of gender gap is complicating.