License activation is done from the management server’s service account (maybe network service, or maybe a designated user account if a service account was used). The connection is made via a normal outbound HTTPS connection so you usually don’t have to make any ACL changes in the network to allow the outbound network connection. Sometimes outbound connections are heavily filtered on locked down networks though. Also, it’s common for a proxy server to complicate things. There are no proxy server settings in the software - the settings in windows are used - for example if you’ve already authenticated with the proxy server after connecting through Internet Explorer, those proxy server settings are typically used by the .NET components the Management Server is using to make the outbound connection.
The license activation is performed against a service at https://www.milestonesys.com.