Working with laboratory animals requires daily contact of mice with the handler. At that moment the most common method to handle laboratory mice is to pick up and restrain the mouse by tail. Picking up by tail is known to cause the anxiety and stress. The animal, which is under pressure during the experiment, will not express its natural behavior. This can have an impact on the results. There are two new methods of handling that led to voluntary approach and low anxiety. These are handling by tunnel and cupping mice on the open hand. In the B. Sc. Thesis we tried to confirm positive influence of both new methods. We performed all handling methods of handling for nine consecutive days. We made the interaction test on the first, fifth and ninth day. We determine the influence of each method by measuring the time that mice stay in interaction with the handler. In the experiment, we used three different lines and both genders. So we were able to analyse the influence of the line and gender to the different handling methods. Results showed the best responses to the handling by tunnel, followed by open hand and as expected the last picking up by tail.